The compound 2-(2,2-dicyclohexylethyl)piperidine, known by its generic name perhexiline, is a well-established chemical entity. In the form of its maleate salt it is used for the prevention of angina pectoris in patients with coronary artery disease. Perhexiline maleate can be represented by the following chemical structural formula: ##STR1##
In the past, perhexiline (I) has been prepared by reacting .alpha.-picoline (II) with phenyl-lithium to form .alpha.-picolyl-lithium. The .alpha.-picolyl-lithium is not isolated but condensed with dicyclohexyl ketone (III) to form .alpha.,.alpha.-dicyclohexyl-2-pyridineethanol (IV). Dehydration of the pyridineethanol using a conventional dehydrating agent, such as phosphoric acid (85%), alcoholic hydrogen chloride or hydrogen bromide results in the preparation of 2-(2,2-dicyclohexylethenyl)pyridine (V), as shown in U.S. Pat. No. 3,038,905. Hydrogenation of the pyridine ring and the double bond to form perhexiline is accomplished using low pressure hydrogen (4 atmospheres) in the presence of a platinum oxide catalyst, as disclosed in British Pat. No. 1,025,578. This reaction sequence can be depicted as follows: ##STR2##
The fully aromatic intermediates have also been previously prepared. Thus, a refluxing mixture of .alpha.-picoline (II), benzophenone (VI) and lithium amide yields .alpha.,.alpha.-diphenyl-2-pyridineethanol (VII) in accordance with the procedure set forth by Tilford et al., J. Am. Chem. Soc. 76, 2431, 2434 (1954). Dehydration of the pyridineethanol with dilute hydrochloric acid or 48 percent HBr results in the preparation of 2-(2,2-diphenylethenyl)pyridine (VIII). This reaction sequence can be indicated as follows: ##STR3## Previous attempts, however, to reduce the double bond, pyridine ring and the two phenyl rings of 2-(2,2-diphenylethenyl)pyridine (VIII) in a single step to obtain perhexiline (I) directly have heretofore been unreported.